Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen.
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PMID:A phase II study of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) with G-CSF for breast cancer patients with visceral metastases or hormone-independent tumors: a trial of the Japan Clinical Oncology Group. 939 Feb 10

Breast cancer patients with more than three involved axillary lymph have a high likelihood of relapse after adjuvant therapy. Early results of administration of high-dose chemotherapy (HDCT) and autologous peripheral blood progenitor cells (PBPC) to patients with primary breast cancer and > or = 10 involved axillary nodes have been encouraging. We performed a multicenter trial to determine whether HDCT could be safely administered to patients with primary breast cancer involving 4-9 axillary lymph nodes. Fifty-four patients with stage II or III breast cancer and 4-9 involved axillary lymph nodes received doxorubicin-based induction chemotherapy, followed by high-dose cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (450 mg/m2) and PBPC mobilized by sargramostim (GM-CSF) or filgrastim (G-CSF). After completion of HDCT, patients received radiation therapy to the chest wall or involved breast, plus tamoxifen. Survival and disease-free survival, time to engraftment, and charges associated with HDCT were determined. Plasma concentrations of BCNU were determined and plasma AUC(BCNU) was calculated. Fifty-four patients were evaluable for survival and relapse-free survival. Fifty-two patients received HDCT with PBPC support and were evaluable for toxicity. Fifteen patients (29%) developed late pulmonary drug toxicity, which resolved with a 10-week course of corticosteroids in all but one affected patient, who subsequently died of pulmonary toxicity. Ten patients relapsed a median of 426 days (range 86-1117 days) after the start of induction chemotherapy, seven of whom have died. Forty-three patients are alive and breast cancer-free at a median of 947 days (range 661-1730 days) after the start of therapy, including one patient who developed myelodysplastic syndrome 809 days after the start of HDCT. Actuarial 4-year survival and disease-free survival from the start of treatment are 84 and 71%, respectively. Mean plasma AUC(BCNU) was 400 (range 82-1255) microgxmin/ml and was not statistically different from that measured in historical controls who received 600 mg/m2 of BCNU. Combined hospital and physician charges for patients treated at the University of Colorado decreased from a mean of $125845 for the first four patients to $77126 for the final seven patients. We conclude that HDCT with autologous PBPC can be administered with acceptable safety to patients with primary breast cancer involving 4-9 axillary lymph nodes. An ongoing, prospective randomized trial is evaluating the efficacy of HDCT for this patient group.
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PMID:High-dose chemotherapy with autologous peripheral blood progenitor cell support for primary breast cancer in patients with 4-9 involved axillary lymph nodes. 942 71

Dendritic cells (DCs), which are antigen presenting cells of potential use in human antitumor vaccination trials, are presently the subject of intense investigation. Many recent studies have reported the possibility of generating ex vivo large numbers of DCs with high antigen presenting capacity by the culture of bone marrow or blood progenitors. In this study, we examined the differentiation into DCs of CD34+ progenitors isolated from the G-CSF mobilized blood of 3 healthy donors and 5 patients with breast cancer and cultured in the presence of GM-CSF + IL-13. The characteristics of the cells were compared to those of cells obtained in the presence of GM-CSF + TNF alpha. By day 15, one third of the bulk cells cultured with IL-13 were CD1a+/CD14- and strongly expressed CD1c, CD40, CD80 and HLA-DR. In contrast, cells obtained with TNF alpha expressed CD1a on one in three cells but with a considerably lower fluorescence intensity than on IL-13-cultured cells and strongly expressed CD14 on more than 50% of cells. CD1a+/CD14- cells emerged in IL-13 cultures at day 5, while in TNF alpha cultures CD14+ cells appeared before CD1a+ cells. Cells grown in the presence of IL-13 had an increased capacity to present antigens to autologous lymphocytes and to stimulate allogeneic T-lymphocytes. This effect was greater than that of cells grown in the presence of TNF alpha. These cells should therefore have greater effector potential in any therapeutic applications in humans.
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PMID:IL-13 induces CD34+ cells isolated from G-CSF mobilized blood to differentiate in vitro into potent antigen presenting cells. 943 67

The feasibility and safety of the administration of multiple cycles of dose-intensive chemotherapy (CT) supported with repeated reinfusions of circulating progenitor cells (CPCs) were evaluated in a prospective study of adjuvant initial therapy of poor-prognosis breast cancer. Eighteen patients with resectable breast cancer involving >/= 10 axillary nodes or >/= 5 axillary nodes and negativity of the estrogen receptor status received a cycle of standard FEC regimen (5-FU 600 mg/m2, epirubicin 60 mg/m2, CTX 600 mg/m2, i.v. on day 1) followed by G-CSF as CPC mobilization technique. Collected CPCs were fractionated and reinfused, with G-CSF, after each of the 4 subsequent cycles of high-dose FEC (HD-FEC) (5-FU 750 mg/m2, epirubicin 120 mg/m2, CTX 3 g/m2, i.v.) planned at 21 day intervals. The median numbers of CD34+ cells and CFU-GM collected (with one or two leukaphereses per patient) were 9.7x10(6)/kg (range: 2.5-22.9) and 9.9x10(4)/kg (range: 1.9-27.3), respectively, and day 9 was the median first day of procedure (range: 8-12) after FEC. All patients received the 4 courses of HD-FEC (for a total of 72 cycles). Hemopoietic recovery was rapid after each cycle and there was no treatment-related delays in CT administration. Mucositis was the major non-hematological toxicity. There were 2, 3, 7 and 9 episodes of WHO grade 3/4 mucositis in cycles 1, 2, 3 and 4, respectively. These severe episodes lasted a median of 4 days (range: 2-6) but no patient required parenteral nutrition. The mean +/- SD total hospital stay lasted 10 +/- 2 days. The delivery of 4 cycles of dose-intensive FEC CT supported by CPCs (mobilized with a single course of standard-dose FEC + G-CSF) is feasible and safe. It could represent an effective alternative strategy to other more aggressive programs for the adjuvant therapy of high-risk early breast cancer.
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PMID:Multicyclic dose-intensive chemotherapy with circulating progenitor cell support for high-risk primary breast cancer. 946 73

37 patients with advanced breast cancer resistant to anthracyclines were treated with paclitaxel 200 mg/m2 by 3-h infusion and carboplatin at an area under the curve of 7 mg.min/ml every 4 weeks with G-CSF support. There were 5 (14%, 95% CI 3-25%) complete and 11 (30%, 95% CI 15-45%) partial responders. Median duration of response was 11.5 months (range 5.2-16.8+), median time to progression 8 months (range 0.26-16.8+) and median survival 12 months (range 0.5-19.6+). Grade 3-4 leucopenia (27%), thrombocytopenia (10%) and diarrhoea (5%) were noted. In conclusion, the combination of paclitaxel and carboplatin is active and well tolerated in patients with advanced breast cancer resistant to anthracyclines.
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PMID:Paclitaxel by 3-h infusion and carboplatin in anthracycline-resistant advanced breast cancer. A phase II study conducted by the Hellenic Cooperative Oncology Group. 947 Aug 53

To support multicyclic, dose-intensive chemotherapy in breast cancer, we assessed the effects of reinfusing hematopoietic progenitors either as a leukapheresis product or as mobilized unprocessed whole blood. In this clinical study, 16 consecutive female breast cancer patients were given six cycles of chemotherapy regimen EC (epirubicin (150 mg/m2) and cyclophosphamide (1250 mg/m2) on day 1). In the first cycle, 24 h after chemotherapy, mobilization of the peripheral blood progenitor cells (PBPC) was started with growth factor G-CSF (Neupogen; Amgen-Roche) at a dose of 5 microg/kg/day for 13 days. In all other cycles G-CSF had been given at the same dose from day 7. On days 11, 12 and 13 the leukaphereses were performed and their products cryopreserved. On day 14 whole blood was collected. The median peak incidence of CFU-GM (granulocyte-macrophage colony-forming unit) in peripheral blood was approximately 50 times the baseline level. The leukapheresed PBPC were divided into portions and reinfused after the fourth, fifth and sixth chemotherapy courses. The support with mobilized whole blood was given after the second and third cycles. The effects of the support of whole blood vs leukapheresed PBPC on hematopoietic recovery were compared. The best yields of leukaphereses were achieved on day 13 after initiation of the chemotherapy. The mean number of CD34+ cells was 4.93 x 10(6)/kg (s.d. 2.7; range 0.36-10.54 x 10(6)/kg) the amount of CFU-GM was 2.18 x 10(5)/kg (s.d. 1.3; range 0.07-4.2 x 10(5)/kg). The yields of CFU-GM in 450 ml whole blood collected on day 14 reached 0.51 x 10(5)/kg (s.d. 0.28; range 0.05-1.5 x 10(5)/kg) and of CD34+ cells were 1.3 x 10(6)/kg (s.d. 0.8, range 0.18-2.58 x 10(6)/kg). PBPC yields in 450 ml of unprocessed whole blood were in some cases not sufficient for good hematopoietic recovery after the EC cycles. Grade 4 leukopenias and thrombocytopenias were two times higher in cycles with whole blood support than in cycles with cryopreserved PBPC support. An increase of PBPC harvest can be simply achieved by collecting larger amounts of unprocessed blood, as used by some authors.
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PMID:Mobilization of peripheral blood progenitor cells (PBPC) through a combination of chemotherapy and G-CSF in breast cancer patients and a possibility of unprocessed whole blood collection. 948 27

Doxorubicin for four cycles plus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for eight cycles is an effective adjuvant regimen for breast cancer patients with more than three involved axillary lymph nodes. We reviewed the incidence of dose delays and growth factor requirements when this regimen is administered to patients receiving concurrent irradiation. Thirty-six patients with more than three involved axillary lymph nodes were treated with the sequential regimen doxorubicin-CMF and irradiation. Patients with two or more dose delays received G-CSF treatment. Seventy-five percent of the patients required dose delays for day-22 neutropenia, and growth factors were needed for half of the patients in order to maintain a received dose intensity of 0.940. The first delayed cycle occurred in 74% of the patients while receiving concomitant chemoradiotherapy. Frequent dose delays were required when the sequential regimen doxorubicin-CMF was administered along with radiotherapy. Growth factors are needed to maintain dose intensity similar to that achieved in the original trial.
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PMID:Frequent dose delays and growth factor requirements with the sequential doxorubicin-CMF schedule. 949 86

G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.
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PMID:Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial. 982 88

From February 1992 to November 1993, forty patients with operable breast cancer tumors larger than three centimeters were enrolled in this study of accelerated neo-adjuvant chemotherapy. Thirty-seven patients are evaluable: one patient was excluded from the protocol and two refused to continue treatment after the first cycle. Chemotherapy consisted of three presurgical cycles of CNF [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5-fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg s.c./day on days 7-12). Twenty-six of 37 patients (70%) achieved objective tumor response and were submitted to quadrantectomy. Toxicity was easily manageable. After a median 55-month follow-up (range 48-70), no locoregional recurrences were observed. Distant metastases occurred in 12/37 (32%) patients. The five-year disease-free (DFS) and overall (OS) survival were 58% and 80%, respectively. Accelerated CNF plus G-CSF proved to be a safe and tolerable regimen yielding a good clinical response thereby increasing the possibility of breast conservation surgery for patients otherwise candidates for mastectomy.
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PMID:Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast cancer tumors larger than three centimeters: a pilot study. 953 46

A seventy-one year-old woman suffered from Stage IIIb advanced breast cancer complicated with direct thoracic invasion and skin eruption. An indwelling intra-arterial catheter was inserted into the subclavian artery for the administration of anti tumor agents. After three courses of neoadjuvant chemotherapy combined with G-CSF and/or PBSCT reinfusion, the breast cancer revealed a remarkable size reduction and was absent from direct thoracic and pectoral muscle, invasion within the physical status and visual analysis by CT scan. Thereafter, the patient underwent a radical mastectomy. In the pathological findings of the operation specimen, despite a remarkable tumor collapse, the microscopic invasion remained in the shallow layer of the pectoral muscle. Thus, the patient should be given additional postoperative irradiation. The patients has had six months of stable tumor-free survival since the mastectomy.
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PMID:[A case report of neoadjuvant intra-arterial injection chemotherapy combined with peripheral blood stem cell reinfusion in an advanced breast cancer patient]. 957 72


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